Nitrogen Doped Carbon Dots for Intracellular Redox Modulation Optical Stimulation

Overview

Journal J Mater Chem B

Publisher Royal Society of Chemistry

Date 2025 Jan 13

PMID 39801498

Authors

P Lagonegro

C Marzuoli

G Tullii

F Rossi

C Bellacanzone

E Mancinelli

F Turco

B M Squeo

M Pasini

M R Antognazza

Affiliations

Soon will be listed here.

Abstract

Carbon dots (CDs) are promising candidates as oxygen photosensitizers, in cancer therapeutic applications due to their high quantum yield, superior chemical and photostability, low cytotoxicity and ease of chemical functionalization/tuning. Nitrogen doping can further improve oxygen photosensitization performance. Besides photodynamic therapy, however, the possibility to finely and remotely regulate the intracellular redox balance by using physical stimuli has been attracting more and more interest not only for nanotheranostic application, but also as a novel, fully biocompatible therapeutic tool. Here, we report on the synthesis of nitrogen-doped CDs by solvothermal methods starting from abundant, bioderived, low-cost precursors, and we characterize their interface with cultures of human embryonic kidney (HEK-293) cells, a widely accepted model of non-tumoral cells. While not affecting cell proliferation, synthesized CDs efficiently modulate, under visible light and physiological stress conditions, intracellular calcium ion dynamics and reactive oxygen species concentration, resulting in a 4-fold increase. The reported results may broaden the application of CDs beyond photodynamic therapy, unveiling new opportunities in the field of redox medicine assisted by carbon-based nanomaterials and optical stimulation.

References

Parameswaran R, Koehler K, Rotenberg M, Burke M, Kim J, Jeong K . Optical stimulation of cardiac cells with a polymer-supported silicon nanowire matrix. Proc Natl Acad Sci U S A. 2018; 116(2):413-421. PMC: 6329945. DOI: 10.1073/pnas.1816428115. View

Criado-Gonzalez M, Bondi L, Marzuoli C, Gutierrez-Fernandez E, Tullii G, Ronchi C . Semiconducting Polymer Nanoporous Thin Films as a Tool to Regulate Intracellular ROS Balance in Endothelial Cells. ACS Appl Mater Interfaces. 2023; 15(30):35973-35985. PMC: 10401575. DOI: 10.1021/acsami.3c06633. View

Fehrentz T, Huber F, Hartrampf N, Bruegmann T, Frank J, Fine N . Optical control of L-type Ca channels using a diltiazem photoswitch. Nat Chem Biol. 2018; 14(8):764-767. DOI: 10.1038/s41589-018-0090-8. View

Cai H, Ma J, Xu X, Chu H, Zhang D, Li J . Sulfonated glycosaminoglycan bioinspired carbon dots for effective cellular labelling and promotion of the differentiation of mesenchymal stem cells. J Mater Chem B. 2020; 8(26):5655-5666. DOI: 10.1039/d0tb00795a. View

Zhang Y, Wu M, Wu M, Zhu J, Zhang X . Multifunctional Carbon-Based Nanomaterials: Applications in Biomolecular Imaging and Therapy. ACS Omega. 2019; 3(8):9126-9145. PMC: 6644613. DOI: 10.1021/acsomega.8b01071. View

Criado-Gonzalez M, Marzuoli C, Bondi L, Gutierrez-Fernandez E, Tullii G, Lagonegro P . Porous Semiconducting Polymer Nanoparticles as Intracellular Biophotonic Mediators to Modulate the Reactive Oxygen Species Balance. Nano Lett. 2024; . PMC: 11194851. DOI: 10.1021/acs.nanolett.4c01195. View

Cabre G, Garrido-Charles A, Moreno M, Bosch M, Porta-de-la-Riva M, Krieg M . Rationally designed azobenzene photoswitches for efficient two-photon neuronal excitation. Nat Commun. 2019; 10(1):907. PMC: 6385291. DOI: 10.1038/s41467-019-08796-9. View

Berridge M, Bootman M, Roderick H . Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol. 2003; 4(7):517-29. DOI: 10.1038/nrm1155. View

Negri S, Faris P, Tullii G, Vismara M, Pellegata A, Lodola F . Conjugated polymers mediate intracellular Ca signals in circulating endothelial colony forming cells through the reactive oxygen species-dependent activation of Transient Receptor Potential Vanilloid 1 (TRPV1). Cell Calcium. 2021; 101:102502. DOI: 10.1016/j.ceca.2021.102502. View

10.

Clapham D . Calcium signaling. Cell. 1995; 80(2):259-68. DOI: 10.1016/0092-8674(95)90408-5. View

11.

Briscoe J, Marinovic A, Sevilla M, Dunn S, Titirici M . Biomass-derived carbon quantum dot sensitizers for solid-state nanostructured solar cells. Angew Chem Int Ed Engl. 2015; 54(15):4463-8. DOI: 10.1002/anie.201409290. View

12.

Sies H, Jones D . Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020; 21(7):363-383. DOI: 10.1038/s41580-020-0230-3. View

13.

Savva A, Hama A, Herrera-Lopez G, Schmidt T, Migliaccio L, Steiner N . Photo-Chemical Stimulation of Neurons with Organic Semiconductors. Adv Sci (Weinh). 2023; 10(31):e2300473. PMC: 10625067. DOI: 10.1002/advs.202300473. View

14.

Fernando K, Sahu S, Liu Y, Lewis W, Guliants E, Jafariyan A . Carbon quantum dots and applications in photocatalytic energy conversion. ACS Appl Mater Interfaces. 2015; 7(16):8363-76. DOI: 10.1021/acsami.5b00448. View

15.

Singh R, Patel K, Mahapatra C, Kang M, Kim H . C-Dot Generated Bioactive Organosilica Nanospheres in Theranostics: Multicolor Luminescent and Photothermal Properties Combined with Drug Delivery Capacity. ACS Appl Mater Interfaces. 2016; 8(37):24433-44. DOI: 10.1021/acsami.6b07494. View

16.

Amal N, Shiddiq M, Armynah B, Tahir D . High reactive oxygen species produced from fluorescence carbon dots for anticancer and photodynamic therapies: A review. Luminescence. 2022; 37(12):2006-2017. DOI: 10.1002/bio.4388. View

17.

Sies H, Berndt C, Jones D . Oxidative Stress. Annu Rev Biochem. 2017; 86:715-748. DOI: 10.1146/annurev-biochem-061516-045037. View

18.

Tullii G, Gutierrez-Fernandez E, Ronchi C, Bellacanzone C, Bondi L, Criado-Gonzalez M . Bimodal modulation of angiogenesis with photoactive polymer nanoparticles. Nanoscale. 2023; 15(46):18716-18726. DOI: 10.1039/d3nr02743k. View

19.

Cailotto S, Mazzaro R, Enrichi F, Vomiero A, Selva M, Cattaruzza E . Design of Carbon Dots for Metal-free Photoredox Catalysis. ACS Appl Mater Interfaces. 2018; 10(47):40560-40567. DOI: 10.1021/acsami.8b14188. View

20.

Wu S, Zhou R, Chen H, Zhang J, Wu P . Highly efficient oxygen photosensitization of carbon dots: the role of nitrogen doping. Nanoscale. 2020; 12(9):5543-5553. DOI: 10.1039/c9nr10986b. View